The present invention relates to delivery methods, systems and components thereof for use with hazardous or toxic pharmaceutical substances, and especially to delivery and injection methods, systems and components thereof for use with radiopharmaceutical substances.
As used herein, the term xe2x80x9cpharmaceuticalxe2x80x9d refers to any substance to be injected or otherwise delivered into the body (either human or animal) in a medical procedure and includes, but is not limited, substances used in imaging procedures (for example, contrast media) and therapeutic substances. A number of such pharmaceutical substances pose a danger to both the patient and the personnel administering the substance if not handled and/or injected properly. Examples of hazardous pharmaceuticals include, but are not limited to, radiopharmaceuticals, biological pharmaceuticals, chemotherapeutic pharmaceuticals and gene therapeutic pharmaceuticals.
Examples of use of a radiopharmaceutical include positron emission tomography (PET) and single-photon emission computerized tomography (SPECT), which are noninvasive, three-dimensional, imaging procedures that provide information regarding physiological and biochemical processes in patients. The first step in producing PET images or SPECT images of, for example, the brain or another organ, is to inject the patient with a dose of the radiopharmaceutical. The radiopharmaceutical is generally a radioactive substance that can be absorbed by certain cells in the brain or other organ, concentrating it there. For example, fluorodeoxyglucose (FDG) is a normal molecule of glucose, the basic energy fuel of cells, to which is attached a radionuclide or radioactive fluor. The radionuclide is produced in a cyclotron equipped with a unit to synthesize the FDG molecule.
Cells (for example, in the brain), which are more active in a given period of time after an injection of FDG, will absorb more FDG because they have a higher metabolism and require more energy. The radionuclide in the FDG molecule suffers a radioactive decay, emitting a positron. When a positron collides with an electron, an annihilation occurs, liberating a burst of energy in the form of two beams of gamma rays in opposite directions. The PET scanner detects the emitted gamma rays to compile a three dimensional image.
In that regard, after injecting the radiopharmaceutical, the patient is typically placed on a moveable bed that slides by remote control into a circular opening of the scanner referred to as the gantry. Positioned around the opening, and inside the gantry, are several rings of radiation detectors. Each detector emits a brief pulse of light every time it is struck with a gamma ray coming from the radionuclide within the patient""s body. The pulse of light is amplified, by a photomultiplier, and the information is sent to the computer that controls the apparatus.
The timing of injection is very important. After the generation of the radiopharmaceutical, a countdown begins. After a certain time, which is a function of the half-life of the radionuclide, the radiation level of the radiopharmaceutical dose falls exactly to a level required for the measurement by the scanner. In current practice, the radiation level of the radiopharmaceutical volume or dose is typically measured using a dose calibrator. Using the half-life of the radionuclide, the time that the dose should be injected to provide the desired level of radioactivity to the body is calculated. When that time is reached, the radiopharmaceutical dose is injected using a manually operated syringe.
Most PET radionuclides have short half-lives. Under proper injection procedures, these radionuclides can be safely administered to a patient in the form a labeled substrate, ligand, drug, antibody, neurotransmitter or other compound normally processed or used by the body (for example, glucose) that acts as a tracer of specific physiological and biological processes.
Excessive radiation to technologists and other personnel working in the scanner room can pose a significant risk, however. Although the half-life of the radiopharmaceutical is rather short and the applied dosages are themselves not harmful to the patient, administering personnel are exposed each time they work with the radiopharmaceuticals and other contaminated materials under current procedures. Constant and repeated exposure over an extended period of time can be harmful.
A number of techniques used to reduce exposure include minimizing the time of exposure of personnel, maintaining distance between personnel and the source of radiation and shielding personnel from the source of radiation. In general, the radiopharmaceuticals are typically delivered to a nuclear medicine facility from another facility equipped with a cyclotron in, for example, a lead-shielded container. Often, the radiopharmaceutical is manually drawn from such containers into a shielded syringe. See, for example, U.S. Pat. No. 5,927,351 disclosing a drawing station for handling radiopharmaceuticals for use in syringes. Remote injection mechanisms can also be used to maintain distance between the operator and the radiopharmaceutical. See, for example, U.S. Pat. No. 5,514,071, disclosing an apparatus for remotely administering radioactive material from a lead encapsulated syringe.
In one procedure, the radiopharmaceutical is injected into tubing that is coiled within a lead container. Typically, the shielded syringe used to inject the radiopharmaceutical is disconnected and replaced by a larger syringe, filled in most cases with saline, for injection into the body and flush. By emptying the second syringe, the radiopharmaceutical is flushed through the shielded, coiled tubing in the container and injected into the person to be scanned. An excess volume of saline supplies a flushing function.
Although substantial effort is made to reduce exposure of administering and other personnel to harmful radiation, some exposure is experienced under current procedures. Being in the injection room longer than necessary is thus to be avoided. Moreover, the cumulative radiation exposure resulting from multiple injection procedures must be closely monitored to avoid overexposure. Indeed, personnel that administer radiopharmaceuticals are typically periodically rotated out of such duties to reduce the risk of overexposure.
In addition to the difficulties introduced by the hazardous nature of radiopharmaceuticals, the short half-lives of such radiopharmaceuticals further complicate the administration of a proper dosage to a patient. As discussed above, initial calibration of radioactivity is often made and the injection is then timed so that a dose of the desired level of radioactivity to the body is delivered (as calculated from the half-life of the radiopharmaceutical). See, for example, U.S. Pat. No. 4,472,403 in which a motor driven syringe is controlled to inject a quantity of a radiopharmaceutical stored in the syringe by calculating the injection quantity based upon the half-life of the radiopharmaceutical and the delay before injection.
Radiation detectors have also been placed upon syringe shields and in line with the radiopharmaceutical delivery system. For example, U.S. Pat. No. 4,401,108 discloses a syringe loading shield for use during drawing, calibration and injection of radiopharmaceuticals. The syringe shield includes a radiation detector for detecting and calibrating the radioactive dosage of the radiopharmaceutical drawn into the syringe. U.S. Pat. Nos. 4,562,829 and 4,585,009 disclose strontium-rubidium infusion systems and a dosimetry system for use therein. The infusion system includes a generator of the strontium-rubidium radiopharmaceutical in fluid connection with syringe for supplying pressurized saline. Saline pumped through the strontium-rubidium generator exits the generator either to the patient or to waste collection. Tubing in line between the generator and the patient passes in front of a dosimetry probe to count the number of disintegrations that occur. As the flow rate through the tubing is known, it is possible to measure the total activity delivered to the patient (for example, in milliCuries). Likewise, radiation measurements have been made upon blood flowing through the patient. For example, U.S. Pat. No. 4,409,966 discloses shunting of blood flow from a patient through a radiation detector.
The danger to administering personnel and other difficulties that arise from the nature of hazardous pharmaceuticals such as radiopharmaceuticals often affect the quality and safety of the injection procedure. For example, given the care that must be taken to prevent radiation overexposure (including limiting the duration of injection procedures), the concern with properly timing an injection and the need to prevent the creation of radioactive wastes, it is often difficult to properly eliminate air from all fluid paths before an injection begins.
It is thus very desirable to develop devices, systems and methods through which toxic or hazardous pharmaceuticals (for example, radiopharmaceuticals) can be administered in controlled manner to enhance their effectiveness and patient safety, while reducing exposure of administering personnel to such hazardous pharmaceuticals.
In one aspect, the present invention provides a method of injecting a hazardous pharmaceutical comprising the steps of: connecting a source of flushing fluid to a first port of a fluid delivery set; connecting a pressurizing unit of a powered injector system (including a powered injector and the pressurizing unit) to a second port of the fluid delivery set; purging air from the fluid delivery set; and, after purging air from the fluid delivery set, connecting a third port of the fluid delivery set to a source of the hazardous pharmaceutical. The fluid delivery set can, for example, include a valve system or assembly to control flow of fluid through the fluid delivery set. The ports of the fluid delivery set can, for example, include luer connectors as known in the medical arts to form a removable, secure and generally sealed connection.
The method preferably further includes the steps of (i) removably connecting a disposable fluid path that is connectable (via, for example, a catheter) to a patient to the fluid delivery set and (ii) purging air from the disposable fluid path before connecting the fluid delivery set to the source of hazardous pharmaceutical.
By removing air from the fluid delivery set and the patient fluid path before any connection is made to the source of hazardous pharmaceutical, exposure of administering personnel to the hazardous pharmaceutical to that point is eliminated. Connecting the fluid delivery set to the source of pharmaceutical can be automated or otherwise accomplished remotely (for example, with use of an extending or robotic arm as known in the machine and robotic arts) to prevent exposure during that connection.
The pressurizing unit can, for example, be a syringe in operative connection with the powered injector. In the case that the pressurizing unit is a syringe, the method can further include the steps of drawing the hazardous pharmaceutical into the syringe and injecting the hazardous pharmaceutical through the fluid delivery set and the disposable fluid path. Using a powered injector having a control unit removed in distance or shielded from the position of the syringe, fluid delivery set and fluid path prevents exposure of operating/administering personnel to the hazardous pharmaceutical. The method preferably further includes the step of flushing the fluid delivery set and the disposable fluid path after injection using the flushing fluid (for example, saline and/or another biologically acceptable flushing agent). A powered injector can also be used with a saline syringe in a similar manner as described above to limit exposure of operating personnel to the hazardous pharmaceutical.
In the case that the hazardous pharmaceutical is a radiopharmaceutical, the method can further include the step of measuring the level or dosage of radioactivity of the radiopharmaceutical injected. Preferably, the level of radioactivity or dosage is measured very near in time or simultaneously with delivery of the radiopharmaceutical to provide an accurate measurement of the dosage delivered. For example, the level of radioactivity can be measured by positioning the syringe within a dose calibrator. The level of radioactivity can also be measured by placing a radioactivity detector in operative connection with a line through which the radiopharmaceutical is dispensed or delivered.
In another aspect, the present invention provides a system for delivery of a hazardous pharmaceutical including: a syringe in operative connection with a powered injector and a protective container to enclose the syringe during operation thereof. The protective container is constructed or adapted to protect personnel from detrimental effects of the pharmaceutical. The system preferably also includes at least one source of flushing fluid; a fluid path adapted to connect to a patient; at least one source of the pharmaceutical; and a fluid delivery set. The fluid delivery set preferably includes a valve assembly to which the syringe, the source of flushing fluid, the fluid path and the source of pharmaceutical are removably connectable.
The valve assembly preferably provides flow control through the fluid delivery set such that operator contact with the fluid delivery set is not required after connection of the source of pharmaceutical to the fluid delivery set. The valve assembly also preferably provides flow control through the fluid delivery set such that the entire fluid delivery set can be purged of air with the syringe and the source of flushing fluid in fluid connection with the valve assembly before the source of pharmaceutical is connected to the fluid delivery set. In one embodiment, the valve assembly includes a bypass line in continuous fluid connection between the source of flushing fluid and the fluid path.
In the case that the pharmaceutical is a radiopharmaceutical, the protective container can, for example, be a component of a dose calibrator adapted to measure the level of radioactivity of the pharmaceutical within the syringe. In one embodiment, the syringe is connected to the powered injector via an extending adapter that preferably extends from the powered injector when connected thereto to position the syringe within the protective container.
The adapter can, for example, include an injector attachment member to attach the adapter to a powered injector and a plunger extension fixed in position relative to a powered injector. The plunger extension preferably has a plunger attachment member to attach to a plunger of the syringe. In one embodiment, the adapter also includes a syringe carriage slidably attached to the adapter. The syringe carriage includes a syringe attachment member to removably attach a syringe thereto so that a barrel of a syringe can be moved relative to a plunger thereof to control fluid flow into and out of a syringe.
The above embodiment of an adapter facilitates orientation of the syringe tip or exit of the syringe directed toward the powered injector when the syringe is attached to the syringe attachment member. This orientation can facilitate purging of air from the syringe when the syringe is placed within, for example, a dose calibrator positioned below the injector. In that regard, lead-shielded dose calibrators are often relatively large and heavy and thus positioned most easily near the floor. Moreover, this relative positioning of the injector and dose calibrator assists in limiting exposure of operating/administering personnel by directing any waves of radiation escaping from the dose calibrator upward to the ceiling of the room. Moving the syringe barrel relative to the syringe plunger in the manner described in the above embodiment facilitates use of commercially available injectors and syringes for use therewith by eliminating the need to change/recalibrate the direction and distance the injector drive member must advance or retract to complete a desired operation.
In another aspect, the present invention provides a method of using a powered injector system to inject a radiopharmaceutical into a body. The method includes the steps of: attaching an extending adapter to the front end of the powered injector; the adapter including an injector attachment to place the adapter in operative connection with the powered injector, the adapter also including a syringe attachment to attach a syringe to the adapter to place the syringe in operative connection with the powered injector; and extending the adapter into a radiation shield. As discussed above, the radiation shield can form part of a dose calibrator to measure the radioactivity of radiopharmaceutical within the syringe. In one embodiment, the exit of the syringe is oriented upward relative to the opposite end of the syringe when the syringe is positioned within the dose calibrator to facilitate purging of air from the syringe. As discussed above, the opening through which the syringe passed to enter the dose calibrator is preferably oriented in a direction (for example, upward toward the ceiling) to decrease the likelihood of exposure of personnel to any radiation waves exiting the dose calibrator during use thereof.
In a further aspect, the present invention provides an adapter for use with a powered injector to attach a syringe to the powered injector including: an injector attachment member to attach the adapter to a powered injector and a syringe attachment member spaced from the injector attachment member by a sufficient distance to position a syringe attached to the syringe attachment member within a radiation dose calibrator. Preferably, the adapter facilitates use of commercially available injector systems with commercially available dose calibrators without the requirement of substantial and/or expensive modification thereto.
In another aspect, the present invention provides an adapter for use with a powered injector to attach a syringe to the powered injector including an injector attachment member to attach the adapter to a powered injector and a plunger extension fixed in position relative to a powered injector. The plunger extension has a plunger attachment member to attach to a plunger of the syringe. The adapter further includes a syringe carriage slidably attached to the adapter and including a syringe attachment member to removably attach a syringe thereto so that a barrel of the syringe can be moved relative to a plunger thereof to control fluid flow into and out of the syringe. As discussed above, the syringe can be oriented with a syringe tip thereof directed toward the powered injector when attached to the syringe attachment member.
In another aspect, an adapter includes an attachment member to removably attach the adapter to a powered injector and a syringe carriage slidably attached to the attachment member. The syringe carriage includes a syringe attachment member to which a syringe can be removably attached. The adapter further includes an end member attached a fixed distance from the attachment member. The end member has a plunger extension attached to the end member and extending toward the injector. The plunger extension includes a plunger attachment member on an end thereof opposite the end attached to the end member. The syringe carriage is adapted to move a barrel of the syringe relative to a plunger of the syringe when a syringe is attached to the syringe attachment member and a plunger thereof is attached to the plunger extension member.
In another aspect, the present invention provides a shield for use with a radiopharmaceutical including a housing that is impenetrable by radioactive energy from the radiopharmaceutical. The shield also includes at least one opening in the housing through which an article containing the radiopharmaceutical, which is positioned within the housing, can be viewed. The opening is in visual alignment with a reflective surface in which a viewer can view a reflection of the article. The opening is positioned within the housing such that there is no direct line between the viewer and the article that is not shielded by a portion of the housing. Because radiation energy from radiopharmaceuticals travels in straight lines, the viewer is shielded from exposure to radiation.
In a further aspect, the present invention provides a method of injecting a radiopharmaceutical into a body. The method includes the steps of: positioning a pressurizing unit or device containing a first volume of the radiopharmaceutical within a dose calibrating unit adapted to measure the level of radioactivity of the radiopharmaceutical; and injecting a second volume of the radiopharmaceutical. The second volume is determined through measurement by the dose calibrating unit to provide a desired level of radioactivity. The second volume can, for example, be less than the first volume. In one embodiment, the pressurizing chamber is a syringe in fluid connection with a powered injector.
In another aspect, the present invention provides a kit for injecting a hazardous pharmaceutical into a body including: a fluid path adapted to connect to a patient; and a fluid delivery set. The fluid delivery set includes a valve assembly to which a pressurizing unit, a source of flushing fluid, the fluid path and a source of the pharmaceutical are removably connectable. The valve assembly provides flow control through the fluid delivery set such that operator contact with the fluid delivery set is not required after connection of the source of pharmaceutical to the fluid delivery set. The valve assembly also preferably provides flow control through the fluid delivery set such that the entire fluid delivery set can be purged of air with the syringe and the source of saline in fluid connection with the valve assembly before the source of pharmaceutical is connected to the fluid delivery set.
In still a further aspect, the present invention provides a method of injecting a radiopharmaceutical into a patient. The method comprises the steps of: connecting a powered pressurizing device that is controlled without intimate or close contact by an operator (for example, remotely controlled, automated or preprogrammed so that the operator is not within a radiation field of a dangerous level) to a valve assembly of a fluid delivery set; connecting at least one source of a flushing fluid to the valve assembly; connecting a patient fluid path to the valve assembly, the patient fluid path terminating in a patient connector; connecting a source of a ready-made (that is, prepared earlierxe2x80x94for example, in an offsite cyclotron) radiopharmaceutical to the valve assembly; and controlling the valve assembly at least during injection of the hazardous pharmaceutical such that operator presence in the vicinity of the radiopharmaceutical is not required. In general, a dose to an individual decreases with the square of the distance from the radiation source. Thus, close operator contact with the pressurizing device, fluid delivery set and other components of the fluid delivery system is not required when the radiopharmaceutical is present in the fluid delivery system. Moreover, shielding as described above can also be used to prevent exposure. The valve assembly can also be controlled without intimate contact by an operator (for example, remotely controlled, automated or preprogrammed).
In general, the present invention provides for administration or delivery of a toxic or hazardous pharmaceuticals (for example, radiopharmaceuticals) in controlled manner to enhance the effectiveness of the pharmaceutical and to enhance patient safety (as compared to current procedures and equipment for delivering such pharmaceuticals), while reducing exposure of administering personnel to the hazardous pharmaceuticals. In general, commercially available injector systems are readily adaptable for use in the present invention without substantial or expensive modification.